To correlate scleral rigidity and corneal stiffness parameters with induced elevation of intraocular pressure (IOP) in healthy subjects using an ophthalmodynamometer. A combined calculation of applanation and indentation tonometric measurements using the Calixto nomogram was used to estimate scleral rigidity (SR) in healthy adults. The stiffness parameter (at first applanation - SP-A1), stress-strain index (SSI), and central corneal thickness were determined using the Corvis ST. Then, all eyes underwent acute IOP elevation through ocular compression using an ophthalmodynamometer at four crescent steps. Univariate and multivariate regression analyses were used to investigate the association between intraocular pressure increase and ocular biomechanical parameters. Fifty-four eyes from 27 participants were included (mean age, 55.9 ± 9.9 years). The mean baseline IOP was 12.9 mmHg. The average values for SR, SP-A1, and SSI were 0.025 AU, 113.8 mmHg/mm, and 1.28, respectively. During ocular compression, IOP significantly increased in all eyes (mean change, 22.4 ± 4.3 mmHg; p < 0.001). The multivariable analysis showed that the magnitude of the rise in IOP was correlated only with SR (coefficient= 178.35; p = 0.03). Scleral, but not corneal, biomechanical parameters correlate independently with the magnitude of acute IOP increase in healthy eyes. These findings support further biomechanical studies involving patients with glaucoma to better understand the relationship between ocular compliance and its mechanical response to different IOP levels.